1 Natural Course of HIV Infection HAIVN Harvard Medical School AIDS Initiative in Vietnam

2 By the end of this session, participants will be able to: Explain the process that HIV infect the human cell Describe the natural progression of HIV infection Explain the factors that influence the progression of HIV infection Identify the clinical stage according to the World Health Organization (WHO) Learning Objectives

3 How Does HIV Infect the Human Cell?

HIV Life Cycle CD4

Co-receptor CCR5 và CXCR4 CD4 Binding HIV Life Cycle

Fusion HIV Life Cycle

Virion Entry HIV RNA HIV Life Cycle

Reverse transcription HIV DNA HIV Life Cycle

Translocation to nucleus HIV Life Cycle

Integration HIV Life Cycle

Transcription / Translation of HIV mRNA / polyprotein HIV Life Cycle

Protease processing and viral assembly HIV Life Cycle

New Virus Released Vòng đời của HIV

HIV Life Cycle & Mechanism of ARV Reverse Transcriptase Inhibitors (14) Protease Inhibitors (10) Fusion/Entry Inhibitors (2) Integration Inhibitors( 1)

15 HIV test identifies antibodies to the HIV virus in the blood HIV test become positive after HIV infection 1-3 months Results of two additional HIV tests should be confirmed positive before diagnosis of HIV infection Xét nghiệm HIV

16 Antibody tests Rapid ELISA / Rapid EIA (“Rapid test”): Results in 10 minutes to 2 hours Positive results must be confirmed with additional testing Western Blot (WB) Used as a confirmatory test Dry Blood Spot(DBS): Used for early HIV diagnosis for infants by PCR at 4-6 weeks of age Các phương pháp xét nghiệm HIV

17 Two common tests used to assess and monitor HIV patients are: CD4 count Total lymphocyte count (TLC) Testing in HIV patient

18 Plasma HIV RNA levels indicate: the magnitude of HIV replication and the rate of destruction of CD4+ cells CD4 and T cell counts indicate the extent of HIV-induced immune damage already suffered CD4 Count and Viral Load Testing

19 Relationship Between CD4 Counts and HIV Viral Load Slow: 100,000

20 Natural Progression of HIV Disease CD4+ cell Count Asymptomatic HZV OHL OC PPE PCP CMV, MAC TB TB MonthsYears After HIV Infection Acute HIV infectionsyndrome Relative level of Plasma HIV-RNA CD4+ T cells

21 CD4 5yrs10yrs15yrs Long term non-progression Rapid progression Death OI Typical Progression Variable Progression of HIV infection

22 HIV progresses through various stages which include: 1. Primary HIV Infection 2. Latent Period 3. AIDS (advanced HIV Infection) Diễn biến tự nhiên của nhiễm HIV

23 Occurs 2-4 weeks after acquiring HIV infection Symptoms last 1-2 weeks In the US and Europe, 53-93% of patients have symptoms In Vietnam and development country, there’s no data about incidence Primary HIV Infection (1) Incidence

SymptomsRate Fever 95% Muscle/ joint pain 80% Lymphadenopathy 75% Pharyngitis 75% Rash 70% Nausea/vomiting/diarrhea 30-60% Headache 33% Primary HIV Infection: Clinical Manifestations The Sanford Guide to HIV/AIDS Therapy 2005

25 A generalized rash is a common finding: 5-10 mm macular or papular erythematous lesions appears hours after fever starts lasts for 5 – 8 days most often involves the face and trunk typically not pruritic can be accompanied by oral, esophagus, anus and genital ulcerations Primary HIV Infection Rash(1)

Primary HIV Infection: Rash (2)

Primary HIV Infection: Pharyngitis

28 Characterized by gradual decline in CD4 count Patients may be healthy for 5-10 years before symptoms develop Symptoms can develop when CD4 < 500 cells/mm3 OIs develop when CD4 < 200 cells/mm3 Latent Period: Asymptomatic HIV Disease

29 Generally occurs when CD4 < 500 Conditions that may be seen when CD4 count is 200 – 500 include: Generalized lymphadenopathy Prolonged fevers or diarrhea for > 1 month Oral candidiasis Pulmonary tuberculosis Herpes zoster (Zona) Vaginal candidiasis Latent Period: Symptomatic HIV Infection

30 AIDS (Advanced HIV Infection) Criteria for Diagnosis Advanced HIV Infection Any condition under clinical stage 3 or 4 (presumptive or definitive diagnosis) and/or CD4 cell count < 350 cells/mm3 AIDSAny condition under clinical stage 4 (presumptive or definitive diagnosis) or CD4 cell count < 200 cells/mm3 Final stage in the natural progression of HIV Infection Guidelines for the Diagnosis and Treatment of HIV/AIDS. Ministry of Health, 2009.

31 Manifestations of HIV Infection Vary Greatly Some patients with CD4 > 200 can be ill with many symptoms Some patients with low CD4 < 100 can feel healthy with no symptoms at all All patients have decreased immune function and are at risk for OIs when: WHO Clinical Stage 3 or 4, CD4 < 200 TLC < 1200

32 What Factors Affect the Rate of Disease Progression? Speeds disease progression: Age Symptoms during primary HIV Nutritional status Opportunistic infections (eg: TB) High viral load Intravenous drug use? Slows disease progression: OI Prophylaxis with cotrimoxazole Antiretroviral Therapy

Antiviral Therapy (ART) and HIV Progression No ARV 1 ARV 2 ARV 3 ARV % Of patients did not show AIDS or death

34 WHO Clinical Stages

35 WHO Clinical Stage can be used to: Estimate degree of damage done to a patient’s immune system Follow progression of HIV disease Determine when to start: prophylactic treatment with cotrimoxazole antiretroviral therapy (ART) (with or without CD4 count) Giai đoạn lâm sàng theo TCTYTG WHO Clinical Stage should be evaluated at every clinic visit

36 Most typical/common syndromes: Asymptomatic Persistent generalized lymphadenophathy Performance Scale 1: No symtom, Normal activity Stage 1: Asymptomatic

37 Most typical/common syndromes: Moderate unexplained weight loss (< 10% of body weight) Recurrent respiratory infections Zona (Herpes zoster) Papular pruritic eruption (PPE) Performance Scale 2: symptomatic but normal activity Stage 2: Mildly Symptomatic

38 Most typical/common syndromes: severe weight loss (> 10% of body weight) chronic diarrhea for > 1 month Recurrent oral candidiasis Pulmonary tuberculosis Performance Scale 3: symptomatic, in bed < 50% of the time Stage 3: Progressively Symptomatic

39 Most typical/common syndromes: Wasting syndrome due to HIV weight loss> 10% chronic diarrhea unexplained> 1 month prolonged fever unexplained > 1 month OIs Performance Scale 4 : bedridden> 50% of the time Stage 4: Severely Symptomatic

40 Primary HIV Infection phase have very high risk of infection although the test result is usually negative On average, it takes 5-10 years from time of initial HIV infection to become ill or have symptoms AIDS is defined as CD4 <200 or stage 4 according to WHO Clinical Stages CD4 is the best tests to evaluate immune system status Key Points

41 Thank you! Question?